Association of Alcohol Dehydrogenase Genes with Alcohol-Related Phenotypes in a Native American Community Sample

Authors

  • Ian R. Gizer,

    1. From the Department of Psychological Sciences (IRG), University of Missouri, Columbia, Missouri; Department of Biochemistry and Molecular Biology (HJE), Indiana University School of Medicine, Indianapolis, Indiana; Department of Molecular and Integrative Neurosciences (DAG, CLE), The Scripps Research Institute, La Jolla, California; and Departments of Neurology and Genetics (KCW), University of North Carolina, Chapel Hill, North Carolina.
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  • Howard J. Edenberg,

    1. From the Department of Psychological Sciences (IRG), University of Missouri, Columbia, Missouri; Department of Biochemistry and Molecular Biology (HJE), Indiana University School of Medicine, Indianapolis, Indiana; Department of Molecular and Integrative Neurosciences (DAG, CLE), The Scripps Research Institute, La Jolla, California; and Departments of Neurology and Genetics (KCW), University of North Carolina, Chapel Hill, North Carolina.
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  • David A. Gilder,

    1. From the Department of Psychological Sciences (IRG), University of Missouri, Columbia, Missouri; Department of Biochemistry and Molecular Biology (HJE), Indiana University School of Medicine, Indianapolis, Indiana; Department of Molecular and Integrative Neurosciences (DAG, CLE), The Scripps Research Institute, La Jolla, California; and Departments of Neurology and Genetics (KCW), University of North Carolina, Chapel Hill, North Carolina.
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  • Kirk C. Wilhelmsen,

    1. From the Department of Psychological Sciences (IRG), University of Missouri, Columbia, Missouri; Department of Biochemistry and Molecular Biology (HJE), Indiana University School of Medicine, Indianapolis, Indiana; Department of Molecular and Integrative Neurosciences (DAG, CLE), The Scripps Research Institute, La Jolla, California; and Departments of Neurology and Genetics (KCW), University of North Carolina, Chapel Hill, North Carolina.
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  • Cindy L. Ehlers

    1. From the Department of Psychological Sciences (IRG), University of Missouri, Columbia, Missouri; Department of Biochemistry and Molecular Biology (HJE), Indiana University School of Medicine, Indianapolis, Indiana; Department of Molecular and Integrative Neurosciences (DAG, CLE), The Scripps Research Institute, La Jolla, California; and Departments of Neurology and Genetics (KCW), University of North Carolina, Chapel Hill, North Carolina.
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Reprint requests: Dr. C.L. Ehlers, TSRI, 10550 North Torrey Pines Road, SP30-1501, La Jolla, CA 92037; Tel.: 858-784-7058; Fax: 858-784-7409; E-mail: cindye@scripps.edu

Abstract

Background:  Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism.

Methods:  The present study tested for associations between alcohol dependence and related traits and 22 single-nucleotide polymorphisms (SNPs) spanning the 7 ADH genes. Participants included 586 adult men and women recruited from 8 contiguous Native American reservations. A structured interview was used to assess DSM-III-R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms.

Results:  No evidence for association with the alcohol dependence diagnosis was observed, but an SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and an SNP at the 5′ end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (= 0.0018 and 0.0012, respectively). Further, a haplotype analysis of these 2 SNPs suggested that the haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (= 0.000006).

Conclusions:  These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.

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